Original Article Chronic Inhibition of Dipeptidyl Peptidase-4 With a Sitagliptin Analog Preserves Pancreatic -Cell Mass and

Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regula-tor of the actions of incretin hormones, exert antihyper-glycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying ef-fects, specifically to attenuate loss of pancreatic -cell mass and function. Here, we investigated the effects of a potent and selective DPP-4 inhibitor, an analog of sitaglip-tin (des-fluoro-sitagliptin), on glycemic control and pan-creatic -cell mass and function in a mouse model with defects in insulin sensitivity and secretion, namely high-fat diet (HFD) streptozotocin (STZ)-induced diabetic mice. Significant and dose-dependent correction of postprandial and fasting hyperglycemia, HbA1c, and plasma triglyceride and free fatty acid levels were observed in HFD/STZ mic